Unsupervised home spirometry versus supervised clinic spirometry for respiratory disease: a systematic methodology review and meta-analysis

Background: The number of patients completing unsupervised home spirometry has recently increased due to more widely available portable technology and the COVID-19 pandemic, despite a lack of solid evidence to support it. This systematic methodology review and meta-analysis explores quantitative differences in unsupervised spirometry compared with spirometry completed under professional supervision. Methods: We searched four databases to find studies that directly compared unsupervised home spirometry with supervised clinic spirometry using a quantitative comparison (e.g. Bland–Altman). There were no restrictions on clinical condition. The primary outcome was measurement differences in common lung function parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)), which were pooled to calculate overall mean differences with associated limits of agreement (LoA) and confidence intervals (CI). We used the I2 statistic to assess heterogeneity, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence certainty for the meta-analyses. The review has been registered with PROSPERO (CRD42021272816). Results: 3607 records were identified and screened, with 155 full texts assessed for eligibility. We included 28 studies that quantitatively compared spirometry measurements, 17 of which reported a Bland–Altman analysis for FEV1 and FVC. Overall, unsupervised spirometry produced lower values than supervised spirometry for both FEV1 with wide variability (mean difference −107 mL; LoA= −509, 296; I2=95.8%; p<0.001; very low certainty) and FVC (mean difference −184 mL, LoA= −1028, 660; I2=96%; p<0.001; very low certainty). Conclusions: Analysis under the conditions of the included studies indicated that unsupervised spirometry is not interchangeable with supervised spirometry for individual patients owing to variability and underestimation.


Unsupervised definition:
For this review, 'unsupervised' was defined as the participants completing spirometry in the absence of a clinician or other professional support and could be at any location.'Supervised' was defined as the presence of a clinician or other trained professional along with the participant when they completed spirometry, again at any location.

Technical issues
Thirteen of the 28 included studies mentioned technical issues with unsupervised spirometry, but only seven of these studies included more detailed reporting of technical issues in a tabulated fashion (see supplementary material).

Quality of spirometry
We found that 20/28 studies referred to the assessment of the quality of the spirometry technique, and only 8 studies provided detail on the quality of unsupervised spirometry using the ATS/ERS (2005) acceptability criteria.However, it was unclear from these studies whether they used an automated system only or if all curves were reviewed by an expert reader to take into account subjective criteria, for example, looking for cough, glottic closure, obstructive mouthpiece or leak and therefore they do not follow current ATS/ERS technical standards.

Adverse events
Two of the 28 included studies reported on technical issues related to patient symptoms during spirometry.One study(35) reported a patient withdrawal due to technical difficulties and one study(40) reported coughing in 5 patients during spirometry leading to withdrawal.The remaining 26 studies did not provide a report on adverse events.

Cost
None of the included studies reported a cost-analysis of spirometry.

Adherence
Author  90% willing to measure daily lung function for a prolonged period of time. One patient distressed to be confronted with your disease every day. Patients responded that it was very useful for them to see a daily overview of their lung function.Moor 2021 (n= 10)  100% considered the home monitoring application and spirometer easy to use. 0% patients considered home spirometry burdensome. 90% found it pleasant to see an overview of their lung function.70% stated monitoring more insights into their disease course. 100% would recommend home monitoring to other patients  90% would continue the use of the home monitoring.Veit 2020 (n= 47)  Acceptance of home spirometry was high. 4 patients discontinued as unable to perform daily measurements due to dyspnea (elderly patients).Wijbenga 2020 (n= 10)  Patient satisfaction with the PulmoLife Spirometer was high (mean VAS score 7.41.4). Five patients reported occasionally doubting whether to contact the hospital. Patients considered the new online application (mean VAS score, 8.91.5) and the Spirobank SmartSpirometer (mean score, 9.01.7)easy to use. Patients highly appreciated the overview of their lung function (mean score, 9.40.9) and the direct data transfer to healthcare providers (mean score, 9.90.3). 100% preferred the use of the Spirobank SmartSpirometer over the PulmoLife Spirometer, with a difference of 1.41.5 points (p=0.02). 100% would like to continue using the online home monitoring application and would recommend it to others.Russell 2016 (n= 50)  Generally daily spirometry was straightforward to measure. Some spirometry triggered fits of coughing, and reason by some for withdrawing.Concern about cough was also a reason for initial study enrolment. Some patients distressed of seeing their lung function.Moor 2018 (n= 10)  80% pleasant to see their FVC results, 20% were neutral. 100% considered spirometry useful and would recommend it to others,  90% wished to continue home monitoring. Daily home monitoring did not lead to higher anxiety levels (HADS anxiety score at baseline 4.5, score after 4 weeks 4.3, p = 0.57), and quality of life remained stable (K-BILD total score at baseline 59.2, score after 4 weeks 60.3, p = 0.65).Finkelstein 1993 (n= 18)  100% well accepted and is easy to use by all patients.

Morlion 2002 (n= 22)
 Well accepted by all patients but one.

Finkelstein 2000 (n= 32)
 74.2% found the self-testing procedures not complicated. 83.9% found spirometry test "not difficult at all". 87.1% took "little or very little time" to complete. 51.6% did not interfere at all with daily activities. 87.1% would "certainly" like to use in the future and did not find it difficult at all.Moor (n= 46)  95% Would recommend it to others. 89% Better insights in disease course. 88% Feeling reassured. 87% More accessible communication with hospital. Most found it easy and useful, non-burdensome and pleasant to see results.

Technical issues:
Author Risk of bias was deemed serious as one study had an unclear or high risk of bias in at least one domain.Imprecision was deemed as serious due to large LoA.Other considerations were deemed serious due to small number of studies.
LoA: Limits of Agreement.CI: Confidence Intervals.GRADE Working Group grades of evidence: High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

1. Home spirometry = 21 2 .Domain 2 :Domain 3 :Domain 4 :
Remote spirometry = 4 (1 excluded as non-English) 3. Home "lung function" = 30 4. Remote "lung function" = 2 Total number of search results: 56 Number of duplicates removed: 11 Total number outside of Covidence: 45 Reference lists of systematic reviews (23 rd August 2021): Total number references screened: 316 Number of duplicates removed: 4 Total number to screen in Covidence: 22 Reference lists of included studies (22 nd November 2021): Total number references screened: 610 Number of duplicates removed: n/a Total number to screen in Covidence: 2 Additional papers added from other sources (23 rd August 2021): Total number to screen in Covidence: 1 Additional PubMed search to find key terms "portable" and "handheld" (23 rd August 2021): ((((portable [Title]) AND (spirometry[Title])) OR ((handheld[Title]) AND (spirometry[Title]))) OR ((handheld[Title]) AND (spirometer[Title]))) OR ((portable[Title]) AND (spirometer[Title])) Total number of search results: 64 Number of duplicates removed: 3 Total number to screen in Covidence: 61 QUADAS-2 ROB form: Was a case-control design avoided?Yes/No/Unclear Could the selection of patients have introduced bias?RISK: LOW/HIGH/UNCLEAR Index test (unsupervised spirometry) A. Risk of bias Describe the index test and how it was conducted and interpreted: Could the conduct or interpretation of the index test have introduced bias?If HIGH, please explain: RISK: LOW/HIGH/UNCLEAR Reference standard (supervised spirometry) A. Risk of bias Describe the reference standard and how it was conducted and interpreted: Is the reference standard likely to correctly classify the target condition of the study?Yes/No/Unclear Could the reference standard, its conduct, or its interpretation have introduced bias?If HIGH, please explain: Patient flow and timing of tests

A. Risk of bias Describe any patients who did not receive the index test(s) and/or reference standard or who were excluded (number of withdrawals): Describe the time interval between index test(s) and reference standard in the primary analysis: Describe any interventions between index test(s) and reference standard (i.e. different package of care  Was there an appropriate interval between index test(s) and reference standard?
Secondary outcomes (adherence, patient satisfaction/acceptability, technical issues, quality of spirometry, adverse events and cost).
 Did all patients receive a reference standard?Yes/No/Unclear  Did patients receive the same reference standard (same type of spirometer)?Yes/No/Unclear  Were all patients included in the analysis?Yes/No/Unclear Could the patient flow and/or spirometry timing have introduced bias?If HIGH, please explain: RISK: LOW/HIGH/UNCLEAR

/year Methods used for assessment of adherence of home spirometry (wording as per paper) Adherence results (terminology as per paper)
Meta-analyses of forest plots using confidence intervals (Cis)Risk of bias was deemed serious as the majority of studies (13/17) had an unclear or high risk of bias in at least one domain.Inconsistency was deemed as serious due to high heterogeneity (I 2 = 96%).Imprecision was deemed as very serious due to large LoA.Other considerations were deemed serious due to publication bias.Risk of bias was deemed serious as the majority of studies had an unclear or high risk of bias in at least one domain.Inconsistency was deemed as serious due to high heterogeneity (I 2 = 99.7%).Imprecision was deemed as serious due to large LoA.Other considerations were deemed serious due to publication bias.